In silico and in vitro anti-AChE activity investigations of constituents from Mytragyna speciosa for Alzheimer’s disease treatment,Journal of Computer-Aided Molecular Design

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In silico and in vitro anti-AChE activity investigations of constituents from Mytragyna speciosa for Alzheimer’s disease treatment
Journal of Computer-Aided Molecular Design ( IF 3.0 ) Pub Date : 2021-01-13 , DOI: 10.1007/s10822-020-00372-4
Wansiri Innok ₁ , Asadhawut Hiranrat ₁ , Netnapa Chana ₁ , Thanyada Rungrotmongkol _{2,

3} , Panita Kongsune ₁

Affiliation

Acetylcholinesterase (AChE), one of the major therapeutic strategies for the treatment of Alzheimer's disease (AD) is to increase the acetylcholine (ACh) level in the brain by inhibiting the biological activity of AChE. In this present work, a set of alkaloids and flavonoids against AChE enzyme were screened by computational chemistry techniques. The docking results showed that among alkaloid compounds the oxindole alkaloid namely mitragynine oxidole B (MITOB) and the indole alkaloids namely mitragynine (MIT) exhibited a good binding affinity towards AChE. These two compounds were then studied by molecular dynamics (MD) simulations. The binding free energy calculation and ligand–protein binding pattern suggested that both alkaloids could interact with AChE very well. Since MIT is the main alkaloid constituent of Mytragyna speciose leaves, this compound was isolated from M. speciose leaves and tested for anti-AChE activity. As a result, the isolated MIT had an inhibitory activity with pIC₅₀ value of 3.57. This finding provided that the mitragynine compound has the potential to be as a therapeutic agent for further anti-AChE drug development in treatment of Alzheimer’s disease.

Graphic abstract

中文翻译：

用于治疗阿尔茨海默病的 Mytragyna speciosa 成分的计算机模拟和体外抗 AChE 活性研究

乙酰胆碱酯酶 (AChE) 是治疗阿尔茨海默病 (AD) 的主要治疗策略之一，是通过抑制 AChE 的生物活性来增加大脑中的乙酰胆碱 (ACh) 水平。在目前的工作中，通过计算化学技术筛选了一组针对 AChE 酶的生物碱和黄酮类化合物。对接结果表明，在生物碱化合物中，羟吲哚生物碱即mitragynine oxidole B (MITOB)和吲哚生物碱即mitragynine (MIT)对AChE表现出良好的结合亲和力。然后通过分子动力学 (MD) 模拟研究这两种化合物。结合自由能计算和配体-蛋白质结合模式表明两种生物碱都可以与 AChE 很好地相互作用。由于 MIT 是生物碱的主要成分Mytragyna speciose叶，这种化合物是从M. speciose叶子中分离出来的，并测试了抗 AChE 活性。结果，分离的MIT具有pIC ₅₀值为3.57的抑制活性。这一发现表明帽柱木碱化合物有可能作为治疗剂用于进一步开发治疗阿尔茨海默病的抗 AChE 药物。

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更新日期：2021-01-13

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